Iron is essential for life due to its role in one-electron redox chemistry in the electron transport chain and as a cofactor in heme and iron-sulfur cluster containing proteins. However, it also represents a potentially dangerous electron-transporting catalytic system that is able to induce oxidative damage through the Fenton reaction. In the Fenton reaction, iron reacts with hydrogen peroxide (H2O2) to produce hydroxyl radical, the most reactive and toxic of the reactive oxygen species (ROS). Iron is prevented from reacting with H2O2 by storage within proteins such as ferritin. At the same time a small amount of redox-active iron exists in the intracellular labile iron pool, making this accessible ferrous iron dangerous under conditions of cellular oxidative stress. Moreover, superoxide and H2O2 are able to release iron from its storage proteins, increasing the labile iron pool and creating a vicious cycle of ROS production.
Elevated iron levels are found in the retinas of patients with age-related macular degeneration, suggesting that iron may play a role in the pathogenesis of AMD. Likewise, patients with the rare hereditary disease aceruloplasminemia have iron overload of the brain, retina, and pancreas, leading to degeneration in these organs. The retinal degeneration in these patients resembles an early onset form of the blinding disease age-related macular degeneration (AMD).
AMD causes severe, irreversible vision loss and is the leading cause of blindness in individuals older than 50 years in the Western World. Macular degeneration is a clinical term that is used to describe a family of diseases that are all characterized by a progressive loss of central vision associated with abnormalities of Bruch's membrane, the choroid, the neural retina and/or the retinal pigment epithelium. These disorders include very common conditions that affect older subjects (age-related macular degeneration or AMD) as well as rarer, earlier-onset dystrophies that in some cases can be detected in the first decade of life. Other maculopathies include North Carolina macular dystrophy, Sorsby's fundus dystrophy, Stargardt's disease, pattern dystrophy, Best disease, and Malattia Leventinese
Age-related macular degeneration (AMD), the most prevalent macular degeneration, is associated with progressive diminution of visual acuity in the central portion of the visual field, changes in color vision, and abnormal dark adaptation and sensitivity. Two principal clinical manifestations of AMD have been described as the dry, or atrophic, form, and the wet, or exudative, form. The most significant risk factor for the development of both forms are age and the deposition of drusen, abnormal extracellular deposits, behind the retinal pigment epithelium (RPE). Drusen causes a lateral stretching of the RPE monolayer and physical displacement of the RPE from its immediate vascular supply, the choriocapillaris. This displacement creates a physical barrier that may impede normal metabolite and waste diffusion between the choriocapillaris and the retina.
Thus, identification and use of survival-promoting factors for the retinal pigment epithelium (RPE), would potentially be of great importance for the treatment and prophilaxis of pathological conditions which result in blindness due to apoptosis of the RPE.